This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bronchial asthma afflicts more than 10% of the U.S. population, and the incidence and prevalence are on the rise. A critical feature of the disease is structural changes in the wall of the airways, which become more prominent as the disease progresses, and are correlated with disease severity and symptoms. It is not clear whether these changes are a normal response to an abnormal injury, or whether the response itself is abnormal. In addition, there is inadequate information describing the mechanisms of airway remodeling to determine whether the structural changes are reversible. The major changes in the airway wall include mucus cell hyperplasia, subepithelial fibrosis, angiogenesis, and smooth muscle cell hyperplasia. We are developing in vitro models to address all of these features, with a central hypothesis that the bronchial epithelial cell orchestrates and modulates each of these processes.